title: Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification biasin cancer observational comparative effectiveness research.
abstract: OBJECTIVE
  Radical cystectomy (RC) is the standard treatment for muscle-invasive urothelial carcinoma of the bladder. Trimodality bladder-preserving therapy (BPT) is an alternative to RC, but randomized comparisons of RC versus BPT have proven infeasible. To compare RC versus BPT, we undertook an observational cohort study using registry and administrative claims data from the Surveillance, Epidemiology and End Results-Medicare database.
  
  
  METHODS
  We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC (n = 1426) or BPT (n = 417). We examined confounding and stage misclassification in the comparison of RC and BPT by using multivariable adjustment, propensity score-based adjustment, instrumental variable (IV) analysis, and simulations.
  
  
  RESULTS
  Patients who received BPT were older and more likely to have comorbid disease. After propensity score adjustment, BPT was associated with an increased hazard of death from any cause (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.05-1.53) and from bladder cancer (HR 1.31; 95% CI 0.97-1.77). Using the local area cystectomy rate as an instrument, IV analysis demonstrated no differences in survival between BPT and RC (death from any cause HR 1.06; 95% CI 0.78-1.31; death from bladder cancer HR 0.94; 95% CI 0.55-1.18). Simulation studies for stage misclassification yielded results consistent with the IV analysis.
  
  
  CONCLUSIONS
  Survival estimates in an observational cohort of patients who underwent RC versus BPT differ by analytic method. Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC, while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. bekelman@uphs.upenn.edu
authors.forename: Justin E
authors.initials: JE
authors.lastname: Bekelman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Handorf
authors.forename: Thomas
authors.initials: T
authors.lastname: Guzzo
authors.forename: Craig
authors.initials: C
authors.lastname: Evan Pollack
authors.forename: John
authors.initials: J
authors.lastname: Christodouleas
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Resnick
authors.forename: Samuel
authors.initials: S
authors.lastname: Swisher-McClure
authors.forename: David
authors.initials: D
authors.lastname: Vaughn
authors.forename: Thomas
authors.initials: T
authors.lastname: Ten Have
authors.forename: Daniel
authors.initials: D
authors.lastname: Polsky
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D057186:Comparative Effectiveness Research; D003198:Computer Simulation; D015986:Confounding Factors, Epidemiologic; D015653:Cystectomy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D006278:Medicare; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D057216:Propensity Score; D012189:Retrospective Studies; D018426:SEER Program; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000601:surgery*